Severe COVID-19 after liver transplantation, surviving the pitfalls of learning on-the-go: Three case reports

BACKGROUND The novel coronavirus 2019(COVID-19)pandemic has dramatically transformed the care of the liver transplant patient.In patients who are immunosuppressed and with multiple comorbidities,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been associated with increased severity and mortality.The main objective of this report is to communicate our experience in the therapeutic management of SARS-CoV-2 infection in 3 liver transplant patients.Secondly,we stress the management and investigation of the contagious spreading into a liver transplant ward.CASE SUMMARY The patients were two women(aged 61 years and 62 years)and one man(aged 68 years),all of them having recently received a liver transplant.All three patients required intensive care unit admission and invasive mechanical ventilation.Two of them progressed severely until death.The other one,who received tocilizumab,had a good recovery.In the outbreak,the wife of one of the patients and four healthcare professionals involved in their care were also infected.CONCLUSION We illustrate in detail the evolution of a nosocomial COVID-19 outbreak in a liver transplant ward.We believe that these findings will contribute to a better understanding of the natural history of the disease and will improve the treatment of the liver transplant patient with COVID-19.

In vitro intracellular IFNγ, IL-17 and IL-10 producing T cells correlates with the occurrence of post-transplant opportunistic infection in liver and kidney recipients

AIM To validate intracellular cytokine production functional assay as means of cell-mediated immunity monitoring of post-transplant patients with opportunistic infection(OI).METHODS Intracellular cytokine-producing CD4^+ and CD8^+ T-cell monitoring was carried out in 30 liver transplant(LTr) and 31 kidney transplant(KTr) recipients from 2010 to 2012. Patients were assessed in our Department of Immunology at the Clinical University ‘Hospital Virgen de la Arrixaca-IMIB' in Murcia, Spain for one year following transplantation. FACS Canto Ⅱ flow cytometer was employed to quantify the intracellular production of IL-17, IFNγ and IL-10 cytokines on stimulated CD4^+CD69^+ and CD8^+CD69^+ T cells and BD FACS DIVA v.6 software was used to analysed the data. Statistical analysis was carried out using SPSS 22.0.RESULTS LTr with OI had significantly lower % of CD8^+CD69^+IFNγ^+T cells at 60(7.95 ± 0.77 vs 26.25 ± 2.09, P < 0.001), 90(7.47 ± 1.05 vs 30.34 ± 3.52, P < 0.001) and 180(15.31 ± 3.24 vs 24.59 ± 3.28, P = 0.01) d posttransplantation. Higher % of CD4^+CD69^+IL-10^+ as well as CD4^+CD69^+IL-17^+ T cells were yet reported at 30(14.06 ± 1.65 vs 6.09 ± 0.53, P = 0.0007 and 4.23 ± 0.56 vs 0.81 ± 0.14, P = 0.005; respectively), 60(11.46 ± 1.42 vs 4.54 ± 0.91, P = 0.001 and 4.21 ± 0.59 vs 1.43 ± 0.42, P = 0.03; respectively) and 90 d(16.85 ± 1.60 vs 4.07 ± 0.63, P < 0.001 and 3.97 ± 0.43 vs 0.96 ± 0.17, P = 0.001). Yet, KTr with OI had significantly lower percentage of CD4^+CD69^+IFNγ^+ at 30(11.80 ± 1.59 vs 20.64 ± 3.26, P = 0.035), 60(11.19 ± 1.35 vs 15.85 ± 1.58, P = 0.02), 90(11.37 ± 1.42 vs 22.99 ± 4.12, P = 0.028) and 180(13.63 ± 2.21 vs 21.93 ± 3.88, P = 0.008) d post-transplantation as opposed to CD4^+CD69^+IL-10^+ and CD8^+CD69^+IL-10^+ T cells which percentages were higher at 30(25.21 ± 2.74 vs 8.54 ± 1.64, P < 0.001 and 22.37 ± 1.35 vs 17.18 ± 3.54, P = 0.032; respectively), 90(16.85 ± 1.60 vs 4.07 ± 0.63, P < 0.001 and 23.06 ± 2.89 vs 10.19 ± 1.98, P = 0.002) and 180(21.81 ± 1.72 vs 6.07 ± 0.98, P < 0.001 and 19.68 ± 2.27 vs 10.59 ± 3.17, P = 0.016) d posttransplantation. The au ROC curve model determined the most accurate cut-off values to stratify LTr and KTr at high risk of OI and Cox Regression model confirmed these biomarkers as the most significant risk factors to opportunistic infection.CONCLUSION Post-transplant percentages of T-cell subsets differed significantly amongst infected-and non-infected-LTr and-KTr and yet this imbalance was found to contribute towards a worst clinical outcome.